Evaluation of the potassium adsorption capacity of a potassium adsorption filter during rapid blood transfusion.

The concentration of extracellular potassium in red blood cell concentrates (RCCs) increases during storage, leading to risk of hyperkalemia. A potassium adsorption filter (PAF) can eliminate the potassium at normal blood transfusion. This study aimed to investigate the potassium adsorption capacity of a PAF during rapid blood transfusion. We tested several different potassium concentrations under a rapid transfusion condition using a pressure bag. The adsorption rates of the 70-mEq/l model were 76·8%. The PAF showed good potassium adsorption capacity, suggesting that this filter may provide a convenient method to prevent hyperkalemia during rapid blood transfusion.

Construction and molecular characterization of a T-cell receptor-like antibody and CAR-T cells specific for minor histocompatibility antigen HA-1H.

The genetic transfer of T-cell receptors (TCRs) directed toward target antigens into T lymphocytes has been used to generate antitumor T cells efficiently without the need for the in vitro induction and expansion of T cells with cognate specificity. Alternatively, T cells have been gene-modified with a TCR-like antibody or chimeric antigen receptor (CAR). We show that immunization of HLA-A2 transgenic mice with tetramerized recombinant HLA-A2 incorporating HA-1 H minor histocompatibility antigen (mHag) peptides and ß2-microglobulin (HA-1 H/HLA-A2) generate highly specific antibodies. One single-chain variable region moiety (scFv) antibody, #131, demonstrated high affinity (KD=14.9 nM) for the HA-1 H/HLA-A2 complex. Primary human T cells transduced with #131 scFV coupled to CD28 transmembrane and CD3ζ domains were stained with HA-1 H/HLA-A2 tetramers slightly more intensely than a cytotoxic T lymphocyte (CTL) clone specific for endogenously HLA-A2- and HA-1 H-positive cells. Although #131 scFv CAR-T cells required >100-fold higher antigen density to exert cytotoxicity compared with the cognate CTL clone, they could produce inflammatory cytokines against cells expressing HLA-A2 and HA-1 H transgenes. These data implicate that T cells with high-affinity antigen receptors reduce the ability to lyse targets with low-density peptide/MHC complexes (~100 per cell), while they could respond at cytokine production level.

Review canine tuberculosis - An emerging concern.

Canine mycobacterial disease was first recognised over 100 years ago but is now an emerging concern. All reported cases of tuberculous disease in dogs have been caused by infection with one of three Mycobacterium tuberculosis-complex (MTBC) organisms (M. tuberculosis, Mycobacterium bovis, and Mycobacterium microti). Molecular PCR and interferon-gamma release assays offer alternative or complementary diagnostic pathways to that of specialist culture, which is limited by availability, sensitivity, and the time it takes to get a result. Optimised triple antimicrobial protocols offer an excellent chance of a successful outcome in dogs where treatment can be considered and is attempted. In this review, the clinical presentation, diagnosis, treatment, and prognosis of canine tuberculosis are discussed.

Canine tuberculosis: A review of 18 new and 565 previously reported confirmed cases.

Cases of canine tuberculosis, a zoonotic infection of significant public health significance, are typically only sporadically reported in the literature. For this observational study, case details were collated both retrospectively and prospectively for dogs infected with Mycobacterium tuberculosis-complex (MTBC) organisms. A total of 18 previously unreported cases as well as 565 historically reported confirmed cases were reviewed. A variety of diagnostic techniques were used to make a confirmed diagnosis of tuberculosis (culture, interferon-gamma release assay [IGRA], and PCR). The reference standard for diagnosis is culture; however, this was negative or not attempted in some dogs. Where fully speciated, all cases were caused by infection with one of three MTBC organisms: M. tuberculosis, Mycobacterium bovis, or Mycobacterium microti. This study includes the first documented canine infections with M. microti in the UK. All cases were assigned to one of four clinical groups based on the presenting signs: 44.1% were primarily pulmonary, 14.5% were primarily abdominal, and the remainder were disseminated or miscellaneous. The development of adjunctive tests remains necessary to support early treatment decisions pending reporting of culture for MTBC organisms, which can take weeks to months. Definitive treatment, where attempted, was successful in most cases. Of the 13 dogs treated by the authors with triple combination antimicrobial therapy, a good clinical outcome was seen in 12 (92%) of them.

Hepatic Gene Expression of Angiogenic and Regeneration Markers in Cats with Congenital Portosystemic Shunts (CPSS).

Congenital portosystemic shunts (CPSS) are vascular anomalies resulting in liver hypoplasia and hepatic insufficiency. Cats with CPSS typically show signs of hepatic encephalopathy associated with increased ammonia, inflammatory cytokines, and oxidative stress. Surgical attenuation of the CPSS results in improved liver function, resolution of clinical signs, and increased portal blood flow. Hepatic gene expression has not previously been investigated in cats with CPSS. Here, we compared the hepatic expression of genes involved in the urea cycle (CPS1, NAGS), angiogenesis (VEGFR2, NPPA, NPR1, NPPC, NPR2, HIF1a), liver regeneration (SERPINB1, HGF, TGFß), and metabolism (FGF21) from a small series of cats (n = 18) with CPSS to that of control cats (n = 10). The expression of TGFß, VEGFR2, HGF, FGF21, and CPS1 was significantly elevated in liver biopsies from cats with CPSS. Cats that could only tolerate partial closure of their CPSS had increased hepatic expression of SERPINB1, HIF1a, and NPR2 compared with those that could tolerate complete ligation. Furthermore, there were no significant correlations between gene expression and pre-operative plasma ammonia concentrations in cats with CPSS. The changes in hepatic gene expression in cats with CPSS are in direct contrast to those seen in dogs with CPSS, suggesting alternative mechanisms may be involved in mediating hepatic changes in cats with CPSS.

Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020-2022).

OBJECTIVES: Feline infectious peritonitis (FIP) is a serious disease that arises due to feline coronavirus infection. The nucleoside analogues remdesivir and GS-441524 can be effective in its treatment, but most studies have used unregulated products of unknown composition. The aim of the present study was to describe the treatment of FIP using legally sourced veterinary-prescribed regulated veterinary compounded products containing known amounts of remdesivir (injectable) or GS-441524 (oral tablets). METHODS: Cats were recruited via email advice services, product sales contacts and study publicity. Cats were excluded if they were deemed unlikely to have FIP, were not treated exclusively with the veterinary compounded products, or if there was a lack of cat and/or treatment (including response) data. Extensive cat and treatment data were collected. RESULTS: Among the 307 cats recruited, the predominant type of FIP was most commonly abdominal effusive (49.5%) and then neurological (14.3%). Three treatment protocols were used; remdesivir alone (33.9%), remdesivir followed by GS-441524 (55.7%) and GS-441524 alone (10.4%). The median (range) initial treatment period duration and longest follow-up time point after starting treatment were 84 (1-330) days and 248 (1-814) days, respectively. The most common side effect was injection pain (in 47.8% of those given subcutaneous remdesivir). Of the 307 cats, 33 (10.8%) relapsed, 15 (45.5%) during and 18 (54.5%) after the initial treatment period. At the longest follow-up time point after completion of the initial treatment period, 84.4% of cats were alive. The cats achieving a complete response within 30 days of starting treatment were significantly more likely to be alive at the end of the initial treatment period than those cats that did not. CONCLUSIONS AND RELEVANCE: Legally sourced remdesivir and GS-441524 products, either alone or used sequentially, were very effective in the treatment of FIP in this group of cats. Variable protocols precluded statistical comparison of treatment regimens.

HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype.

Minor histocompatibility (H) antigens are targets of graft-vs-host disease and graft-vs-tumor responses after human leukocyte antigen matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium blocks that encoded novel minor H antigens using the large dataset from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B-lymphoid cell line by minor H antigen-specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single-nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as 'HapMap SNP Scanner', and can incorporate T-cell recognition and other data with genotyping datasets from CEU, JPT, CHB, and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP-based customized therapies.

Effect of an antimicrobial stewardship intervention on the prescribing behaviours of companion animal veterinarians: A pre-post study.

BACKGROUND: Antimicrobial stewardship is a cornerstone of efforts to combat antimicrobial resistance. We evaluated the impact of a formal discussion of antimicrobial stewardship for dogs and cats on systemic antimicrobial prescribing behaviours among companion animal veterinarians. METHODS: Electronic health records including information about the prescription of antimicrobials were collected from a multisite UK veterinary practice between 2017 and 2020. We undertook interrupted time series analysis using a quasi-Poisson model to compare the pre- and postintervention change in level and slope for multiple outcomes. RESULTS: After the intervention, there were sustained reductions in the prescription rate of cefovecin to cats and metronidazole to dogs and increases in amoxicillin-clavulanic acid prescribing. There was no evidence for an immediate change in overall prescribing rates in either species, although rates increased over the 12 months after the intervention. There was a transient increase in the proportion of dogs who had their weight recorded at the time of prescription. Results suggest decreases in the prescription of off-licence antimicrobials in both species and the likelihood of underdosing in dogs. CONCLUSIONS: Discussion of antimicrobial stewardship is more likely to influence the antimicrobial choice than whether to prescribe or not. Interventions may benefit by focusing on appropriate antimicrobial selection rather than overall prescription frequency.

Subarachnoid diverticulum associated with feline infectious peritonitis in a Siberian cat.

CASE SUMMARY: A 7-month-old Siberian cat was presented for investigation of acute onset multifocal neurological deficits. Neurological examination documented dull mental status and an ambulatory left hemiparesis. Serum biochemistry documented marked hyperglobulinaemia. MRI of the brain identified marked leptomeningeal contrast enhancement extending along the brainstem caudally to involve the cranial cervical spinal cord. MRI of the cervical spine further identified a subarachnoid diverticulum that extended from the level of the obex to the C2-C3 vertebrae. Cerebrospinal fluid quantitative RT-PCR was positive for the presence of feline coronavirus. Histopathology revealed pyogranulomatous meningitis and choroid plexitis, uveitis and nephritis. RELEVANCE AND NOVEL INFORMATION: This article describes the first reported case of a subarachnoid diverticulum associated with feline infectious peritonitis.

Evaluation of polymorphisms in inflammatory mediator and cellular adhesion genes as risk factors for feline infectious peritonitis.

OBJECTIVES: Feline infectious peritonitis (FIP) is a high mortality infectious disease. Single nucleotide polymorphisms (SNPs) in the genes encoding interferon gamma (IFNG), tumour necrosis factor alpha (TNFA) and dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) have been associated with increased and decreased risk of developing FIP. This study was designed to determine whether these associations were present in a UK population of pedigree cats using samples from cats euthanased with a confirmed diagnosis (FIP, n = 22; non-FIP, n = 10) or clinically healthy cats over 11 years of age (n = 3). METHODS: DNA was extracted from tissue (n = 32) or blood (n = 3) and PCR performed for regions of IFNG, TNFA and CD209. PCR amplicons were sequenced, each SNP genotype was determined, and genotype/allele frequency for each SNP and FIP status were compared. RESULTS: No significant association was found between the genotype and FIP status for any SNP analysed. There was a trend for the heterozygous CT genotype at both IFNG g.401 and IFNG g.408 to be associated with FIP (P = 0.13), but this genotype was also found in a substantial proportion of non-FIP cats. There was also a trend for the heterozygous CT genotype at IFNG g.428 to be associated with FIP (P = 0.06), although most cats with FIP had the CC genotype at this locus. No associations were found between any allele at TNFA g.-421, CD209 g.1900, CD209 g.2276, CD209 g.2392 and CD209 g.2713 and FIP. CONCLUSIONS AND RELEVANCE: The use of the IFNG, TNFA and CD209 SNPs described to predict the risk of FIP cannot currently be recommended.

Evaluation of Interferon-Gamma Polymorphisms as a Risk Factor in Feline Infectious Peritonitis Development in Non-Pedigree Cats-A Large Cohort Study.

Feline infectious peritonitis (FIP) is a common infectious cause of death in cats, with heritable host factors associated with altered risk of disease. To assess the role of feline interferon-gamma gene (fIFNG) variants in this risk, the allele frequencies of two single nucleotide polymorphisms (SNPs) (g.401 and g.408) were determined for non-pedigree cats either with confirmed FIP (n = 59) or from the general population (cats enrolled in a large lifetime longitudinal study; n = 264). DNA was extracted from buccal swabs or tissue samples. A pyrosequencing assay to characterize the fIFNG SNPs was designed, optimized and subsequently performed on all samples. Genotype and allele frequency were calculated for each population. Characterization of the target SNPs was possible for 56 of the cats with FIP and 263 of the cats from the general population. The SNPs were in complete linkage disequilibrium with each other. There was an association between FIP status and genotype (χ2; p = 0.028), with a reduced risk of developing FIP (χ2; p = 0.0077) associated with the genotype TT at both positions. These results indicate that, although fIFNG variants may be associated with altered risk of disease, the prevalence of individual variants within both populations limits application of their characterization to breeding purposes.

The Effect of Natural Feline Coronavirus Infection on the Host Immune Response: A Whole-Transcriptome Analysis of the Mesenteric Lymph Nodes in Cats with and without Feline Infectious Peritonitis.

Feline infectious peritonitis (FIP) is a coronavirus-induced disease of cats, in which the immune system is known to play a crucial, but complex, role in the pathogenesis. This role is still incompletely understood, with involvement of both host and viral factors. To evaluate differential gene expression and pathway involvement in feline coronavirus (FCoV) infection and FIP, we applied next-generation RNA-sequencing of the mesenteric lymph nodes from cats with naturally-acquired FIP, as well as those with systemic FCoV infection without FIP, and those with neither. Viral infection was associated with upregulation of viral defenses regardless of the disease state, but to a greater degree in FIP. FIP was associated with higher pro-inflammatory pathway enrichment, whilst non-FIP FCoV-positive cats showed lower enrichment of humoral immunity pathways, below that of uninfected cats in the case of immunoglobulin production pathways. This host response is presumed to be protective. In FIP, downregulation of T cell-related processes was observed, which did not occur in non-FIP FCoV-positive cats. These results emphasize the importance of the host's immune balance in determining the outcome of the FCoV infection.

Colony Stimulating Factors in Early Feline Infectious Peritonitis Virus Infection of Monocytes and in End Stage Feline Infectious Peritonitis; A Combined In Vivo And In Vitro Approach.

Feline coronavirus (FCoV) infection initiates monocyte-associated viremia and viral persistence. Virus-infected, -activated monocytes also trigger feline infectious peritonitis (FIP), a fatal systemic disease of felids typified by granulomatous (peri)phlebitis. Currently, the exact mechanisms inducing monocyte activation and FIP are unknown. This study attempted to identify the potential immediate effect of virulent FCoV on colony-stimulating factor (CSF) (granulocyte (G)-CSF, monocyte (M)-CSF and granulocyte-monocyte (GM)-CSF levels through in vitro assessment, alongside prototypical pro- and anti-inflammatory mediators (interleukin (IL)-1, IL-6, IL-12p40, tumor necrosis factor (TNF)-α, and IL-10); this was assessed alongside the in vivo situation in the hemolymphatic tissues of cats euthanized with natural end-stage FIP. For the in vitro work, isolated monocytes from SPF cats were cultured short-term and infected with the FIP virus (FIPV) strain DF2. Mediator transcription was assessed by quantitative reverse transcriptase PCR (RT-qPCR) at 3, 6 and 9 h post infection (hpi), and in the post-mortem samples of bone marrow, spleen, and mesenteric lymph nodes (MLN) of cats with FIP. We observed limited and transient changes in cytokine transcription in monocytes after infection, i.e., a significant increase of IL-6 at 3 hpi and of GM-CSF over the 3 and 6 hpi period, whereas M-CSF was significantly decreased at 9 hpi, with a limited effect of age. The findings indicate that the infection induces expansion of the monocyte/macrophage population, which would ensure the sufficient supply of cells for consistent viral replication. In natural disease, the only upregulation was of G-CSF in the MLN, suggesting either immune exhaustion or an active downregulation by the host as part of its viral response.

Update on Feline Hemoplasmosis.

"The wall-less, hemotropic, mycoplasma species Mycoplasma haemofelis, "Candidatus Mycoplasma turicensis" and, to a lesser extent, "Candidatus Mycoplasma haemominutum" have the potential to induce clinical hemolytic anemia in infected cats. Prevalence varies markedly between infecting species, complicated by a chronic carrier state. Accurate and prompt confirmation of infection and identification of the infecting hemoplasma species enables appropriate antibiotics (eg, tetracycline; fluoroquinolone) to be prescribed. Although cats with hemoplasmosis respond rapidly to antibiosis and supportive care, initial monotherapy treatment rarely results in clearance of infection. A protocol now exists for the clearance of the most pathogenic feline hemoplasma M haemofelis."

Hyperplastic and fibrosing gastropathy resembling Ménétrier disease in a cat.

CASE SUMMARY: A 3.5-year-old domestic shorthair cat presented with a 6 month history of weight loss and polyphagia. Clinical examination revealed a markedly reduced body condition score (2/9) and a quiet demeanour. Laboratory abnormalities comprised a mild non-regenerative anaemia, stress leukogram, hypoproteinaemia due to hypoalbuminaemia, azotaemia, hypokalaemia, total hypocalcaemia and sub-maximally concentrated urine (specific gravity 1.020). Abdominal ultrasonography revealed marked thickening of the gastric mucosa within the fundus, body and pylorus; the most dorsal portion of the fundus was spared. The thickened mucosa contained multiple small, anechoic cyst-like structures. The gastric submucosa, muscularis and serosa appeared normal. Histopathology, performed on a full-thickness gastric biopsy, revealed mucosal hypertrophy and markedly dilated gastric glands in areas; not all gastric glands were affected, with some appearing normal or atrophic. Focal interstitial fibrosis was present in some areas. The findings of hypoproteinaemia, gastric ultrasonographic changes and histopathology results share several similarities to those reported with Ménétrier disease. RELEVANCE AND NOVEL INFORMATION: Ménétrier disease is a rare condition of the stomach in humans. A similar condition, giant hypertrophic gastritis (or Ménétrier-like disease), has also been described rarely in dogs. To our knowledge, Ménétrier-like disease has not been previously described cats. This case shares features of Ménétrier-like disease, raising the suspicion of a similar aetiopathogenesis.

Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD.

Fms-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells. An internal tandem duplication (ITD) of FLT3 (FLT3/ITD) is the most frequent mutation in human adult acute myeloid leukemia (AML). FLT3/ITD contributes to the constitutive activation of FLT3 itself and its downstream signal components, mitogen-activated protein kinase and signal transducers and activators of transcription 5 (STAT5), and enables interleukin (IL)-3-dependent cell lines to grow autonomously. In the present study, we showed the specific association of FLT3/ITD with Lyn, which led to the phosphorylation of Lyn in vivo. We also demonstrated that FLT3/ITD receptors displayed a higher affinity to bind to Lyn than wild-type FLT3 receptors in vitro and that this affinity was relative to the intensity of tyrosil phosphorylation of the receptor. Both treatment with small interfering RNA (siRNA) targeting Lyn and the Src family kinase inhibitor PP2 suppressed the IL-3-independent growth of FLT3/ITD-expressing 32D cells (FLT3/ITD-32D), reducing the constitutive phosphorylation of Lyn and STAT5. PP2 treatment of mice transplanted with FLT3/ITD-32D cells blocked the onset of tumors and decreased the size of established tumors. These results demonstrate that Lyn is an important component of the signal transduction pathway specific to FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD.

Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency.

Genetic analysis of a heterozygous protein C-deficient patient revealed a novel deletion of a single guanine residue (8857G) among four consecutive guanine nucleotides [380Trp(TGG)-381Gly(GGT)] in exon IX, which encodes the carboxyl-terminal region of protein C. This deletion results in a frameshift mutation and substitution of the last 39 amino acids (381Gly-419Pro) with 81 abnormal amino acid residues, and we have designated this elongated variant as Protein C-Nagoya. A mutagenic primer was designed which replaced the third guanine residue upstream from the deletion with cytosine, thereby creating a new AvaI site in an otherwise normal allele. Analysis of the polymerase chain reaction products derived from this mutagenic primer showed that the abnormal allele has been inherited in this family. To elucidate how this molecular abnormality leads to protein C deficiency, an expression plasmid containing this mutation was transfected into COS 7, BHK, and psi-2 cells, and the secretory process of the expressed Protein C-Nagoya was analyzed. ELISA and immunoprecipitation analysis with [35S]methionine labeling indicated that the mutant protein C, which was larger in size than normal, was mostly retained within the cells, and only a small portion of it was secreted into the medium. These results suggest that most of Protein C-Nagoya undergoes degradation within the producing cells, and this frameshift mutation apparently leads to protein C deficiency by impairment of secretion of the elongated protein C into plasma.

High incidence of secondary failure of platelet recovery after autologous and syngeneic peripheral blood stem cell transplantation in acute promyelocytic leukemia.

Secondary failure of platelet recovery (SFPR), which is a delayed decline in platelet count after primary recovery following myeloablative hematopoietic SCT, is a significant problem in allogeneic SCT. However, its clinical characteristics have not been well described in autologous SCT for acute myeloid leukemia. We reviewed 11 consecutive patients who had received autologous or syngeneic SCT for acute promyelocytic leukemia. Seven of 11 patients (64%) had SFPR, which is defined as a decline in the platelet count to less than 30,000/microl for more than 7 days. The median onset of SFPR was day 36 (range, 25-51 days) and the median duration of thrombocytopenia was 13 days (range, 4-25 days). Of nine patients who received busulfan-containing preparative regimens, seven (78%) had SFPR and one had delayed primary platelet count recovery. Neither patient who received cyclophosphamide and total body irradiation as preparative regimens had SFPR. The clinical courses of SFPR were transient and self-limited. SFPR was not associated with relapse of underlying diseases, graft failure or other fatal morbidities. The unexpectedly high prevalence and the characteristics of SFPR may provide additional information on management following autologous SCT for acute myeloid leukemia.

In vitro and in vivo anticancer activity of 2-acetyl-benzylamine isolated from Adhatoda vasica L. leaves.

One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0.40 and 0.39mM at 24h when compared to other tested cells, respectively. Apoptosis was confirmed by annexin V-FITC/PI kit using flow cytometry and confocal microscope in MOLM-14 and NB-4 cells. In addition, 2-acetyl-benzylamine induced cell cycle arrest at G2/M phase in MOLM-14 cells and G0/G1 phase in NB-4 cells. Apoptosis mechanism was confirmed by RT-PCR and Western blot analysis. Treatment with 2-acetyl-benzylamine decreased the Bcl-2 activity and increased the Bax expression; cytochrome c was released and caspases-3 was activated in MOLM-14 and NB-4 cells. Besides, 2-acetyl-benzylamine inhibited the expression of JAK2/STAT3 in MOLM-14 and NB-4 cells. In vivo administration of 2-acetyl-benzylamine inhibited the growth of MOLM-14 cells in xenograft mice model. Molecular docking study has been performed to investigate the binding mode and to estimate the binding energy of 2-acetyl-benzylamine with the active site of JAK-2, AKT1, FLT3 and Bcl-2. The above findings proved that 2-acetyl-benzylamine could be developed as a potential therapeutic agent against cancer.

Different breakage-prone regions on chromosome 1 detected in t(11;14)-positive mantle cell lymphoma cell lines and multiple myeloma cell lines are associated with different tumor progression-related mechanisms.

To better define secondary aberrations that occur in addition to translocation t(11;14)(q13;q32) in mantle cell lymphomas (MCL) and in multiple myelomas (MM), seven t(11;14)-positive MCL cell lines and four t(11;14)-positive MM cell lines were analysed by fluorescence R-banding and spectral karyotyping (SKY). Compared with published data obtained by G-banding, most chromosome aberrations were redefined or further specified. Furthermore, several additional chromosome aberrations were identified. Thus, these cytogenetically well defined t(11;14)-positive MCL and MM cell lines may be useful tools for the identification and characterization of genes that might be involved in the pathogenesis of MCL and MM, respectively. Since MCL and MM were found to have different alterations of chromosome 1, these were investigated in more detail by fluorescence in situ hybridization (FISH) and multicolor banding (MCB) analyses. The most frequently altered and deletion-prone loci in MCL cell lines were regions 1p31 and 1p21. In contrast, breakpoints in MM cell lines most often involved the heterochromatic regions 1p12-->p11, and the subcentromeric regions 1q12 and 1q21. These data are in accordance with previously published data of primary lymphomas. Our findings may indicate that different pathways of clonal evolution are involved in these morphologically distinct lymphomas harboring an identical primary chromosome aberration, t(11;14).